(296 days)
The Omega Laboratories Hair Drug Screening Assay (Opiates, Oxycodone and Hydrocodone) is an in vitro diagnostic test that is intended for the qualitative detection of opiates (calibrated with morphine) and oxycodone and hydrocodone (calibrated with oxycodone) at or above 300 pg/mg in human head and body hair. To confirm a screen positive result. a more specific alternate chemical method, such as Gas ChromatographyMass Spectrometry (GC/MS) operating in the selected ion monitoring (SIM) mode is the preferred method with deuterated internal standards. Professional judgment should be applied to any drug of abuse test result, particularly when presumptive positive results are obtained. This test is intended exclusively for single laboratory use only and is not intended for sale to anyone.
The Omega Laboratories Hair Drug Screening Assays are test systems that utilize ELISA assays for the qualitative detection of morphine and related opiates (calibrated with morphine) and oxycodone and hydrocodone (calibrated with oxycodone) at or above 300 pg/mg in head hair samples. The Omega Laboratories Hair Drug Screening Assay for Opiates, Oxycodone and Hydrocodone provide only preliminary analytical test results. A more specific alternate chemical method must be used in order to obtain a confirmed result. Gas Chromatograph - Mass Spectrometry operating in the selected ion monitoring (SIM) mode or GC/MS/MS in selected reaction mode (SRM) is the preferred method with deuterated internal standards.
Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Device Name: Omega Laboratories Hair Drug Screening Assay (Opiates, Oxycodone and Hydrocodone)
Indications for Use: The device is intended for the qualitative detection of opiates (calibrated with morphine) and oxycodone and hydrocodone (calibrated with oxycodone) at or above 300 pg/mg in human head and body hair. It's for single laboratory use only and not for sale to anyone. A more specific alternate chemical method, such as Gas Chromatography/Mass Spectrometry (GC/MS) operating in the selected ion monitoring (SIM) mode, is the preferred method for confirmation of screen positive results.
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" as a set of quantified thresholds. Instead, it demonstrates performance studies to show "substantial agreement" with a predicate device and ensures reliable qualitative detection at the cutoff. Based on the provided performance studies, here's an interpretation of the implied acceptance and the reported performance.
Implicit Acceptance Criterion: The device should consistently and accurately identify positive and negative samples around the cutoff concentration (300 pg/mg) and show substantial agreement with GC/MS confirmation. It should also demonstrate precision, specificity, and stability under various conditions.
| Performance Characteristic | Implied Acceptance Criteria (Interpretation) | Reported Device Performance (Summary) |
|---|---|---|
| Precision (Intra-assay) | All samples below cutoff should be negative; all samples above cutoff should be positive. Samples at the cutoff and slightly below/above may show variability, but consistency is key. | For Opiates and Oxycodone, all samples from 0 to 225 pg/mg were negative, and all from 375 to 600 pg/mg were positive (11/11). For Hydrocodone, 0-225 pg/mg were negative (except one sample at 225 pg/mg was positive in 1 replicate), and 375-600 pg/mg were positive (10/10). |
| Precision (Inter-assay) | High consistency (all negative below cutoff, all positive above cutoff) over multiple days. | For Opiates and Oxycodone, all samples from 0 to 225 pg/mg were negative (220/220), and all from 375 to 600 pg/mg were positive (220/220). For Hydrocodone, 0 to 150 pg/mg were negative (100/100), and 375 to 600 pg/mg were positive (100/100). At 225 pg/mg (75% below cutoff), 61% were negative and 39% positive, demonstrating variability near cutoff. |
| Agreement with GC/MS (Opiates) | High concordance with GC/MS, especially for high positive and negative samples. Few discordant results, particularly near cutoff. | Out of 226 samples: |
- 208/208 (100%) agreement for Negative (70), 50% above cutoff (116) by GC/MS.
- Near Cutoff Negative (9): 2 Positive by ELISA, 7 Negative by ELISA.
- Near Cutoff Positive (24): 24 Positive by ELISA, 1 Negative by ELISA.
Overall strong agreement, with expected variability near cutoff. Discordant samples were mostly near the cutoff. |
| Agreement with GC/MS (Oxycodone) | High concordance with GC/MS, especially for high positive and negative samples. Few discordant results, particularly near cutoff. | Out of 483 samples (after exclusions): - 361/361 (100%) agreement for Negative (140), 50% above cutoff (221) by GC/MS.
- Near Cutoff Negative (14): 6 Positive by ELISA, 8 Negative by ELISA.
- Near Cutoff Positive (94): 94 Positive by ELISA, 2 Negative by ELISA.
Overall strong agreement, with expected variability near cutoff. Discordant samples were mostly near the cutoff. |
| Agreement with GC/MS (Hydrocodone) | High concordance with GC/MS, especially for high positive and negative samples. Few discordant results, particularly near cutoff. | Out of 500 samples (after exclusions): - 343/343 (100%) agreement for Negative (142), 50% above cutoff (201) by GC/MS.
- Near Cutoff Negative (25): 8 Positive by ELISA, 17 Negative by ELISA.
- Near Cutoff Positive (110): 110 Positive by ELISA, 6 Negative by ELISA.
Overall strong agreement, with expected variability near cutoff. Discordant samples were mostly near the cutoff. |
| Cross-Reactivity | Minimal cross-reactivity with unrelated compounds. Structurally similar compounds may show some cross-reactivity as expected, but this should be characterized. | Detailed tables provided showing percent cross-reactivity for numerous compounds. Structurally similar opiates/opioids show varying degrees of cross-reactivity. Unrelated compounds generally showed no interference at high concentrations (e.g., NEG result at -50% CO for many compounds, turning POS at +125% and +150% CO, indicating no false positive at low concentrations). Specific opiate/oxycodone related compounds did show cross-reactivity, which is characterized. |
| Interfering Compounds | No false positive or false negative results due to common interfering substances that are not drugs of abuse. | For both Opiates and Oxycodone assays, a large panel of structurally related and unrelated compounds were tested. Generally, non-cross-reactive compounds did not cause false positives at relevant concentrations (-50% CO was NEG). Structurally similar compounds that could cross-react turned POS, as expected for the assay. No tested samples produced a negative result when expected to be positive. |
| Calibrator and Control Stability | Calibrators and controls should be stable for a defined period while maintaining accuracy. | Calibrator stock solution for morphine and oxycodone was stable for one year (within 10% of target value). |
| Storage Stability (Hair Samples) | Drug analytes in hair samples should remain stable over reasonable storage periods. | Opiates stable for 3 years; Oxycodone and Hydrocodone stable for 2 years. Mean change in concentration ranged from -5% to +7% for various analytes. |
| Shipping Stability | Temperature and humidity variations during shipping should not adversely affect test results. | Average mean % change in screening result prior to and after shipping was 1.9%. Four out of 260 samples showed different screening results but were all near the cutoff (±50%), where variability is expected. |
| Cosmetic Treatment Effects | Acknowledgement and characterization of the impact of cosmetic treatments on drug detection. The ELISA protocol itself should not introduce new artifacts related to treatment. | Cosmetic treatments can reduce drug amounts. The study shows the ELISA protocol is not an exception. Bleach, Dye, Permanent, Relaxer, and Shampoo treatments all showed varying effects, mostly decreasing concentrations. Changes at cutoff were observed (e.g., Dyeing Opiates: 57 Pos to Neg, 110 Neg to Pos due to change at cutoff level; Shampoo Oxycodone/Hydrocodone: Pos to Neg). Cross-reactivity was noted for specific treatments (e.g., Permanent with Hydrocodone to Opiates). |
| Environmental Contamination | The assay should be able to distinguish between true positive samples and those with external contamination, facilitated by a methanol wash. | Analytically negative samples exposed to drugs remained negative after methanol wash. Clinically positive samples remained positive after methanol wash. This indicates the methanol wash procedure mitigates false positives from external contamination. |
2. Sample Sizes Used for the Test Set and Data Provenance
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Test Set Sample Sizes:
- Intra-assay Precision: 11 replicates per concentration level (for Opiates & Oxycodone), 10 replicates per concentration level (for Hydrocodone).
- Inter-assay Precision: 220 samples per concentration level (for Opiates & Oxycodone), 100 samples per concentration level (for Hydrocodone) tested over 20 non-consecutive days.
- Agreement Studies (with GC/MS):
- Opiates: 226 head and body hair samples (176 head hair, 50 body hair).
- Oxycodone & Hydrocodone: 530 head and body hair samples (240 head hair in Study 1, 240 head hair in Retrospective Study 2, 50 body hair in Study 3). Note: Actual N for Oxycodone was 483 (due to exclusions) and for Hydrocodone was 500 (due to exclusions).
- Cross-reactivity: 3 replicates per compound, per concentration level.
- Interfering Compounds: 3 replicates per compound, per concentration level (-50% CO, +125% CO, +150% CO).
- Storage Stability: 54 samples varying in ethnic origin, hair color, and curvature.
- Shipping Study: 260 head hair samples (155 confirmed positive, 100 screened negative, 5 below cutoff).
- Cosmetic Treatment: 176 hair specimens (112 positive for opiates/oxycodone, 64 negative).
- Environmental Contamination: A set of drug-free hair samples and a set of known positive samples. (Exact numbers not specified, but implied to be sufficient for the qualitative determination described).
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Data Provenance: The document does not explicitly state the country of origin for the human hair samples used in the test sets. It mentions "body and head hair samples from different ages, gender, ethnicities and hair color," but no geographical origin.
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Retrospective/Prospective: The agreement studies included a "retrospective analysis Study 2" for Oxycodone and Hydrocodone, implying some of the data was collected previously. Other studies (Precision, Study 1 for Agreement, Storage, Shipping, etc.) appear to be prospectively conducted for this submission, although this is not explicitly stated.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The ground truth for the test set (agreement studies) was established using Gas Chromatography/Mass Spectrometry (GC/MS) operating in the selected ion monitoring (SIM) mode as the preferred method, with deuterated internal standards. This is an instrumental, objective method, not dependent on human expert interpretation in the same way an imaging study would be. Therefore, the concept of "number of experts" and their "qualifications" for establishing ground truth doesn't directly apply in this context. The validity of GC/MS as a "more specific alternate chemical method" implies its established status as a gold standard in drug testing.
4. Adjudication Method for the Test Set
Since the ground truth for the test set was established by GC/MS, an instrumental method, human adjudication methods like "2+1" or "3+1" are not applicable. The GC/MS results serve as the definitive reference. Discordant results between the ELISA and GC/MS were reported and analyzed, but not "adjudicated" by human experts in the sense of consensus building for ground truth.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
This is an in vitro diagnostic (IVD) hair drug screening assay, not an AI-powered diagnostic imaging device. Therefore, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study focusing on human reader improvement with AI assistance is not relevant and was not performed.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
The device is an ELISA assay, which is a laboratory-based, instrumental test. The results are generated by the assay (the "algorithm" in a chemical sense) detecting the presence of analytes above a cutoff. The "human-in-the-loop" aspect exists in performing the lab procedures, running the instrument, and interpreting the qualitative (positive/negative) output based on the cutoff. The performance studies (precision, agreement) inherently reflect the standalone performance of the assay. There's no separate "human-in-the-loop" performance that would be contrasted with pure "algorithm only" performance beyond the standard lab process.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The primary ground truth used for agreement studies was Gas Chromatography/Mass Spectrometry (GC/MS) operating in the selected ion monitoring (SIM) mode. This is a highly specific and sensitive analytical method widely considered a confirmatory or gold standard in toxicology for identifying and quantifying substances.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of an algorithm or AI model development. This device is an immunoassay (ELISA), which is an analytical chemical test. Its performance is based on the specificity and reactivity of antibodies and other chemical components, not on a machine learning model trained on data. Therefore, the concept of a "training set" as understood in AI/ML is not applicable here. The development and optimization of the assay would typically involve extensive R&D and validation steps, but these are not referred to as "training" in the AI sense.
9. How the Ground Truth for the Training Set Was Established
As explained in point 8, the concept of a "training set" for an AI/ML algorithm does not apply to this ELISA-based in vitro diagnostic device. The ground truth for the validation/performance studies was established by GC/MS, as detailed in point 7.
§ 862.3650 Opiate test system.
(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).